40800-90-6

Basic information

• Product Name: 3-(Methoxymethylene)-2(3H)-benzofuranone
• Synonyms: 3-(A-METHOXY)METHYLENEBENZOFURAN-2(3H)-ONE;3-(METHOXYMETHYLENE)-2(3H)-BENZOFURANONE;3-(methoxymethylidene)-1-benzofuran-2-one
• CAS NO: 40800-90-6
• Molecular Formula: C₁₀H₈O₃
• Molecular Weight: 176.17
• Mol File: 40800-90-6.mol
• Article Data: 14

Chemical Properties

• Boiling Point: 331.1 °C at 760 mmHg
• Flash Point: 136.6 °C
• Appearance: powder
• Density: 1.358 g/cm³
• Vapor Pressure: 0.000159mmHg at 25°C
• Refractive Index: 1.665
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 3-(Methoxymethylene)-2(3H)-benzofuranone(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(Methoxymethylene)-2(3H)-benzofuranone(40800-90-6)
• EPA Substance Registry System: 3-(Methoxymethylene)-2(3H)-benzofuranone(40800-90-6)

Safety Data

• Hazardous Substances Data: 40800-90-6(Hazardous Substances Data)

Usage

Uses

3-(Methoxymethylene)-2(3H)-benzofuranone is an intermediate in the synthesis of Azoxystrobin (A965150), an strobilurin fungicide.

InChI:InChI=1/C10H8O3/c1-12-6-8-7-4-2-3-5-9(7)13-10(8)11/h2-6H,1H3/b8-6-

Synthetic route

benzofuran-2(3H)-one (553-86-6) + trimethyl orthoformate (149-73-5) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
With acetic anhydride at 95 - 100℃; Concentration;	96.5%
With acetic anhydride at 40 - 90℃; Temperature;	96.8%
at 110℃; for 21h; Large scale;
With zinc(II) chloride at 110℃; for 4h;

methanol (67-56-1) + 3-hydroxymethylenebenzofuran-2(3H)-one potassium salt → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
Stage #1: 3-hydroxymethylenebenzofuran-2(3H)-one potassium salt at 10℃; pH=2 - 3; Stage #2: methanol With hydrogenchloride for 4h; Reflux;	95.2%

2-Hydroxyphenylacetic acid (614-75-5) + trimethyl orthoformate (149-73-5) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
Stage #1: 2-Hydroxyphenylacetic acid With acetic anhydride at 100℃; for 2h; Inert atmosphere; Large scale; Stage #2: trimethyl orthoformate at 100℃; for 19h; Time; Large scale;	90%
In 2-Methylpropionic anhydride at 100℃; for 10h;	59%
With 2-Methylpropionic anhydride at 100℃; for 10h;	59%
With acetic anhydride at 80 - 100℃; for 6h;

3-formylbenzofuran-2(3H)-one (40800-88-2) + dimethyl sulfate (77-78-1) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h; Time;	90%

2-Hydroxyphenylacetic acid (614-75-5) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
With acetic anhydride; trimethyl orthoformate In water; acetic acid; toluene
Multi-step reaction with 2 steps 1: acetic anhydride / 2.5 h / 110 °C / Inert atmosphere; Large scale 2: 21 h / 110 °C / Large scale View Scheme
Multi-step reaction with 2 steps 1: acetic acid; phosphorus pentoxide / toluene / 6 h / Reflux 2: zinc(II) chloride / 4 h / 110 °C View Scheme

2-Methylpropionic anhydride (97-72-3) + 2-Hydroxyphenylacetic acid (614-75-5) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
With trimethyl orthoformate

benzofuran-2(3H)-one (553-86-6) + 2-Hydroxyphenylacetic acid (614-75-5) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
With acetic anhydride; trimethyl orthoformate

benzofuran-2(3H)-one (553-86-6) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
With acetic anhydride; trimethyl orthoformate In methanol; dichloromethane
Multi-step reaction with 2 steps 1: sodium hydride / N,N-dimethyl-formamide / 2 h / -10 - 0 °C 2: potassium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: isopropyl alcohol / 20 °C 2.1: sodium hydroxide / methanol / 5 h / 40 °C 2.2: 3 h / Reflux View Scheme

3-(α-hydroxy)methylenebenzofuran-2(3H)-one (70450-82-7) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
With sulfuric acid In methanol

methanol (67-56-1) + 3-diethylaminemethylidene-2-benzofuranone → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
Stage #1: 3-diethylaminemethylidene-2-benzofuranone With sodium hydroxide In methanol at 40℃; for 5h; Stage #2: methanol With sulfuric acid for 3h; Reflux;

3-diethylaminemethylidene-2-benzofuranone + dimethyl sulfate (77-78-1) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
Stage #1: 3-diethylaminemethylidene-2-benzofuranone With sodium hydroxide In methanol; water at 40℃; for 5h; Stage #2: dimethyl sulfate With tetrabutylammomium bromide In methanol; water at 30℃; for 5h;

methanol (67-56-1) + 3-dimethylaminomethylene-2-(3H)benzofuranone → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
Stage #1: 3-dimethylaminomethylene-2-(3H)benzofuranone With sodium hydroxide In methanol at 40℃; for 5h; Stage #2: methanol With sulfuric acid for 3h; Reflux;

dimethyl sulfate (77-78-1) + 3-dimethylaminomethylene-2-(3H)benzofuranone → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
Stage #1: 3-dimethylaminomethylene-2-(3H)benzofuranone With sodium hydroxide In methanol; water at 40℃; for 5h; Stage #2: dimethyl sulfate With tetrabutylammomium bromide In methanol; water at 30℃; for 5h;

2'-chloro-benzeneacetic acid (2444-36-2) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide; copper(II) oxide / water / pH 7 / Autoclave 2: water / 12 h / 100 °C / Autoclave View Scheme

benzofuran-2(3H)-one (553-86-6) + acetic anhydride (108-24-7) + trimethyl orthoformate (149-73-5) → 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6)

Conditions	Yield
In water at 100℃; for 12h; Autoclave;

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → benzofurane-3-carboxylic acid (26537-68-8)

Conditions	Yield
With sodium hydroxide In methanol at 0 - 60℃; Solvent; Reagent/catalyst; Temperature;	97.5%

4,6-dichloropyrimidine (1193-21-1) + 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) + sodium methylate (124-41-4) → 3-((α)‐2‐(2‐(6‐chloropyrimidin-4‐yl)oxy)phenyl)methyl-3-methoxyacrylate (383428-73-7)

Conditions	Yield
In tetrahydrofuran; methanol at 3 - 24℃; for 72h; Temperature; Inert atmosphere; Large scale;	93%

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) + sodium methylate (124-41-4) → 2-(2-hydroxyphenyl)-3,3-dimethoxypropionic acid methyl ester (175971-61-6)

Conditions	Yield
In methanol at -10℃; for 1h; Inert atmosphere;	86%
In methanol at -5 - 0℃; for 1h;	86%

methanol (67-56-1) + 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → 2-(2-hydroxyphenyl)-3,3-dimethoxypropionic acid methyl ester (175971-61-6)

Conditions	Yield
Stage #1: methanol With sodium at -10℃; for 0.5h; Stage #2: 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone for 1h; Inert atmosphere;	86%
With sodium at 0℃; for 1h;

methanol (67-56-1) + 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) + sodium methylate (124-41-4) → 2-(2-hydroxyphenyl)-3,3-dimethoxypropionic acid methyl ester (175971-61-6)

Conditions	Yield
at -5 - 0℃; for 1h;	86%

4,6-dichloropyrimidine (1193-21-1) + 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) + sodium methylate (124-41-4) → 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionic acid methyl ester (143230-42-6)

Conditions	Yield
Stage #1: 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone; sodium methylate With 2-methyl-1,4-divinylpiperazine In methanol; acetonitrile at 15 - 20℃; for 0.5h; Stage #2: 4,6-dichloropyrimidine In methanol; acetonitrile for 1h; Solvent; Temperature;	85%
With 2-methyl-1,4-divinylpiperazine In tetrahydrofuran; methanol at 15 - 20℃; for 5h; Solvent; Temperature; Reagent/catalyst;	80%
Stage #1: 3-(α-methoxy)methylene benzofuran-2-(3H)-ketone; sodium methylate With potassium carbonate In methanol; toluene at 0℃; for 0.416667h; Inert atmosphere; Stage #2: 4,6-dichloropyrimidine With 1,4-diaza-bicyclo[2.2.2]octane In methanol; toluene for 1h; Reagent/catalyst; Temperature; Solvent;	55.2%

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → 3-(α-hydroxy)methylenebenzofuran-2(3H)-one (70450-82-7)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In water
With hydrogenchloride; sodium hydroxide; sulfuric acid In methanol; water

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → sodium salt of 3-(α-hydroxy)methylenebenzofuran-2(3H)-one

Conditions	Yield
With sodium hydroxide In water
With hydrogenchloride; sodium hydroxide; sulfuric acid In methanol; 5,5-dimethyl-1,3-cyclohexadiene; water

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → 3-hydroxymethylenebenzofuran-2(3H)-one potassium salt

Conditions	Yield
With potassium hydroxide In water

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → calcium salt of 3-(α-hydroxy)methylenebenzofuran-2(3H)-one

Conditions	Yield
In water

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → methyl 2-(2-(6-chloro-2-methylpyrimidin-4-yloxy)-phenyl)-3,3-dimethoxypropanoate (1394124-24-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C View Scheme

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → methyl 2-(2-(2,6-dichloropyrimidin-4-yloxy)phenyl)-3,3-dimethoxypropanoate (1394124-25-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C View Scheme

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → methyl 2-(2-(6-chloro-2-(methylthio)pyrimidin-4-yloxy)phenyl)-3,3-dimethoxypropanoate (1394124-26-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C View Scheme

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → methyl 2-(2-(6-chloro-2-(o-tolylthio)pyrimidin-4-yloxy)phenyl)-3,3-dimethoxypropanoate (1394124-27-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C View Scheme

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → methyl 2-(2-(6-chloro-2-(m-tolylthio)pyrimidin-4-yloxy)phenyl)-3,3-dimethoxypropanoate (1394124-28-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C View Scheme

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → methyl 2-(2-(6-chloro-2-(p-tolylthio)pyrimidin-4-yloxy)phenyl)-3,3-dimethoxypropanoate (1394124-29-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C View Scheme

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → methyl 2-(2-(6-chloro-2-(pyridin-2-ylthio)pyrimidin-4-yloxy)phenyl)-3,3-dimethoxypropanoate (1394124-30-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C View Scheme

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → (E)-methyl 2-(2-(6-chloro-2-methylpyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate (1394124-31-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C 3: methanesulfonic acid; acetic anhydride / 2 h / 90 °C View Scheme

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → (E)-methyl 2-(2-(2,6-dichloropyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate (114077-64-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C 3: methanesulfonic acid; acetic anhydride / 2 h / 90 °C View Scheme

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → (E)-methyl 2-(2-(6-chloro-2-(methylthio)pyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate (1394124-32-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C 3: methanesulfonic acid; acetic anhydride / 2 h / 90 °C View Scheme

3-(α-methoxy)methylene benzofuran-2-(3H)-ketone (40800-90-6) → (E)-methyl 2-(2-(6-chloro-2-(o-tolylthio)pyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate (1394124-33-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol / 1 h / -10 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 8 h / 60 °C 3: methanesulfonic acid; acetic anhydride / 2 h / 90 °C View Scheme

Upstream product

• 614-75-5 2-Hydroxyphenylacetic acid 
• 97-72-3 2-Methylpropionic anhydride 
• 553-86-6 benzofuran-2(3H)-one 
• 70450-82-7 3-(α-hydroxy)methylenebenzofuran-2(3H)-one 
• 149-73-5 trimethyl orthoformate 
• 40800-88-2 3-formylbenzofuran-2(3H)-one 
• 77-78-1 dimethyl sulfate 
• 67-56-1 methanol 
• 2444-36-2 2'-chloro-benzeneacetic acid 
• 108-24-7 acetic anhydride 
• 74-87-3 methylene chloride 

Downstream Products

• 70450-82-7 3-(α-hydroxy)methylenebenzofuran-2(3H)-one 
• 1394124-24-3 methyl 2-(2-(6-chloro-2-methylpyrimidin-4-yloxy)-phenyl)-3,3-dimethoxypropanoate 
• 1394124-29-8 methyl 2-(2-(6-chloro-2-(p-tolylthio)pyrimidin-4-yloxy)phenyl)-3,3-dimethoxypropanoate 
• 1394124-30-1 methyl 2-(2-(6-chloro-2-(pyridin-2-ylthio)pyrimidin-4-yloxy)phenyl)-3,3-dimethoxypropanoate 
• 1394124-31-2 (E)-methyl 2-(2-(6-chloro-2-methylpyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate 
• 114077-64-4 (E)-methyl 2-(2-(2,6-dichloropyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate 
• 1394124-32-3 (E)-methyl 2-(2-(6-chloro-2-(methylthio)pyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate 
• 1394124-33-4 (E)-methyl 2-(2-(6-chloro-2-(o-tolylthio)pyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate 
• 1394124-34-5 (E)-methyl 2-(2-(6-chloro-2-(m-tolylthio)pyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate 
• 1394124-35-6 (E)-methyl 2-(2-(6-chloro-2-(p-tolylthio)pyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate 
• 1394124-36-7 (E)-methyl 2-(2-(6-chloro-2-(pyridin-2-ylthio)pyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate 
• 1394124-12-9 (E)-methyl 2-(2-(6-(2-cyanophenoxy)-2-methylpyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate 
• 1394124-13-0 (E)-methyl 2-(2-(2-chloro-6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate 
• 1394124-14-1 (E)-methyl 2-(2-(6-(2-cyanophenoxy)-2-(methylthio)pyrimidin-4-yloxy)phenyl)-3-(methoxy)acrylate 

Relevant articles and documents

Preparation method of 3-hydroxymethylene benzofuran-2(3H)-one and azoxystrobin intermediates

The invention relates to the field of bactericides, and discloses a preparation method of 3-hydroxymethylene benzofuran-2(3H)-one and 3-(alpha-methoxy)-methylene benzofuran-2(3H)-one. The structure of the 3-hydroxymethylene benzofuran-2(3H)-one is as shown in a formula (2). The method comprises the following steps carrying out contact reaction on a compound with a structure as shown in a formula (1) and CO to obtain the compound with the structure as shown in the formula (2). The method provided by the invention is clean in process condition, low in reaction raw material cost and easy to industrialize, and can realize the purpose of green generation;.

Synthesis method of methoxybenzofuranone

The invention discloses a synthesis method of methoxybenzofuranone. The synthesis method comprises the following steps: performing a reaction on o-chlorophenylacetic acid, liquid alkali and a catalyst1, acidifying by using concentrated hydrochloric acid, then distilling for dehydration, cyclizing after completion of the dehydration, then washing with alkali, washing with water and concentrating;performing a reaction on trimethyl orthoformate, acetic anhydride and synthesized benzofuranone, deacidifying, dissolving, washing with water and desolvating after completion of the reaction to obtainthe methoxybenzofuranone. According to the synthesis method, the benzofuranone is firstly synthesized from the o-chlorophenylacetic acid and the methoxybenzofuranone is further synthesized from the benzofuranone, the trimethyl orthoformate and the acetic anhydride; during the reaction, the steps, such as acidifying, dehydrating, washing with the alkali, washing with water and distilling, are continuously carried out, so that not only is the originally synthesized benzofuranone purified and the purity of benzofuranone is improved, but also the purity of the methoxybenzofuranone is improved; after being detecting with high performance liquid chromatography, the purity of the methoxybenzofuranone is as high as 98% or above and the yield can reach 90% or above.

Preparation method of methoxy methene compound

The invention relates to a preparation method of a methoxy methene compound. The preparation method comprises the following steps that (1) under the existence of alkaline substances, a compound shownas a formula (1) is subjected to hydrolysis reaction; salt of a compound show as a formula (III) is prepared; (2) methylation with a conventional methylation reagent is directly performed without separation to prepare the compound shown as a formula (1); or the prepared salt of the compound show as the formula (III) is subjected to acidification to prepare the compound show as the formula (III); then, under the acid catalysis, the compound and methyl alcohol take substitution reaction to prepare the compound shown as the formula (I). The process is simple and convenient; the raw materials canbe easily obtained; the cost is low; the reaction conversion rate is high; the selectivity is high. The formulas are shown in the description, wherein R1 is hydrogen or Cl-C4 alkyls; R2 is Cl-C4 alkyl; n is 0 or 1.